Genome-Wide Association Study of Post-Traumatic Stress Disorder in Two High-Risk Populations

Abstract

Mexican Americans (MAs) and American Indians (AIs) constitute conspicuously understudied groups with respect to risk for post-traumatic stress disorder (PTSD), especially in light of findings showing racial/ethnic differences in trauma exposure and risk for PTSD. The purpose of this study was to examine genetic influences on PTSD in two minority cohorts. A genome-wide association study (GWAS) with sum PTSD symptoms for trauma-exposed subjects was run in each cohort. Six highly correlated variants in olfactory receptor family 11 subfamily L member 1 (OR11L1) were suggestively associated with PTSD in the MA cohort. These associations remained suggestively significant after permutation testing. A signal in a nearby olfactory receptor on chromosome 1, olfactory receptor family 2 subfamily L member 13 (OR2L13), tagged by rs151319968, was nominally associated with PTSD in the AI sample. Although no variants were significantly associated after correction for multiple testing in a meta-analysis of the two cohorts, pathway analysis of the top hits showed an enrichment cluster of terms related to sensory transduction, olfactory receptor activity, G-protein coupled receptors, and membrane. As previous studies have proposed a role for olfaction in PTSD, our results indicate this influence may be partially driven by genetic variation in the olfactory system.

Keywords: American Indians; GWAS; Mexican Americans; PTSD; enrichment analysis; olfaction.

Figure 1

Manhattan plot showing the p-value for sum PTSD symptoms in the Mexican American cohort. Suggestive (blue line) and genome-wide (red line) significance thresholds are p<1.84E-05 and p<9.22E-07, respectively, calculated using the Genetic Type 1 Error Calculator (GEC) software.

Figure 2

Manhattan plot showing the p-value for sum PTSD symptoms in the American Indian sample. Suggestive (blue line) and genome-wide (red line) significance thresholds are p<1.78E-05 and p<8.91E-07, respectively, calculated using the Genetic Type 1 Error Calculator (GEC) software.

Figure 3

Manhattan plot showing the p-value for the fixed effects meta-analysis of the Mexican American and American Indian cohorts; significance thresholds represent the more conservative estimate from the Mexican American cohort. The blue and red lines represent suggestive and genome-wide significance thresholds, respectively.